The present invention relates to 1.alpha., 2.alpha.-methylene-6-methylene- and 6.alpha.-methylpregnenes, processes for the production thereof, and pharmaceutical preparations containing them.
Cyproterone acetate (17-acetoxy-6-chloro-1.alpha.,2.alpha.-methylene-4-pregnene-3,20-dione), described by Wiechert, Neumann et al. (Arzneimittelforschung 17 [1967] 1103, and U.S. Pat. No. 3,423,507, has thus far been the most effective antiandrogen with ovulation-inhibiting (antigonadotropic) activity. It extensively hampers the influence of androgens on their target organs by competitive inhibition. Thus, cyproterone acetate lessens sexual drive in men with sexual deviations and, in the final analysis, represents a medicinial alternative for castration for criminological considerations.
Treatment with cyproterone acetate is of special significance for prostate carcinoma and prostate hypertrophy. It is generally known that androgens convey growth-promoting impetus to the carcinoma of the prostate--just as to the tissue, on the substrate of which it develops. By eliminating the androgen effect with the aid of antiandrogens, the growth of the carcinoma can be inhibited.
The antiandrogenic activity of cyproterone acetate makes it possible to effect specific therapy of androgenization phenomena in females: Favorable effects can be exerted on pathological hairiness in hirsutism, androgenetic alopecia, as well as increased function of the sebaceous glands in case of acne and seborrhea ("Arztliche Praxis" [Medical Practice] 100:3461 [1978]).
Cyproterone acetate was synthesized within the scope of a synthesis program for oral gestagens. The compound shows strong progestational as well as antigonadotropic activities. The strongly progestational activity was demonstrated in the Clauberg test on rabbits, and the antigonadotropic effect was proven in the ovulation inhibiting test on rats.
A combination of cyproterone acetate (gestagen) and ethynylestradiol (estrogen) is available as a preparation for the treatment of androgenization symptoms in women and, at the same time, as a reliable contraceptive for those women who suffer primarly from these symptoms or who develop or show aggravation of acne and similar symptoms when using other ovulation-inhibiting agents.
In all these cases, cyproterone acetate is used systemically. In contrast, topical use of cyproterone acetate does not lead to any substantial success.
It would be desirable to have an agent capable of such topical administration for such uses.